Prediction of h5-HT2A receptor antagonistic activity of arylindoles: Computational approach using topochemical descriptors

Relationship between the topochemical indices and h5-HT2A receptor antagonistic activity of arylindoles has been investigated. Three topochemical indices, Wiener's topochemical index – a distance-based topochemical descriptor, molecular connectivity topochemical index – an adjacency-based topochemical descriptor and eccentric connectivity topochemical index – an adjacency-cum-distance based topochemical descriptor, were used for the present investigation. A data set comprising 31 differently substituted arylindoles was selected for the present study. The values of the Wiener's topochemical index, molecular connectivity topochemical index and eccentric connectivity topochemical index were computed for all the analogues involved in the data set using an in-house computer program. Resultant data was analyzed and suitable models were developed after identification of the active ranges. Subsequently, a biological activity was assigned to each analogue using these models, which was then compared with the reported h5-HT2A receptor antagonistic activity. Accuracy of prediction was found to vary from a minimum of ∼81% to a maximum of ∼84%.